As a recently established tenure track investigator at the NCI, only very preliminary ideas on this project can be presented. We plan to perform chemical and genetic screenings to identify compounds and genes involved in totipotency using pluripotent cells such as mouse embryonic stem cells as a model. For these screens we are currently generating different reporter cell lines. -In addition, we are generating a new mouse model in which we will express in a doxycycline-dependent manner a gene highly expressed in totipotent cells. We follow on the idea that the totipotent state might be relevant somehow during cancer formation and progression. Therefore, by defining the molecular players involved in the maintenance of totipotency we expect by extension, find new ways to understand and thus, attack cancer.